Submissions for variant NM_007294.4(BRCA1):c.1018del (p.Lys339_Val340insTer)

dbSNP: rs80357774

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000030968	SCV000282253	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-22	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000236511	SCV000292507	pathogenic	not provided	2020-11-10	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in association with breast and ovarian cancer (Eccles 1998, Scott 2003, Rebbeck 2018); Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.1137delG; This variant is associated with the following publications: (PMID: 10872502, 12601471, 9649133, 24094589, 28205045, 29446198)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000030968	SCV000324932	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776317	SCV000911644	pathogenic	Hereditary cancer-predisposing syndrome	2021-05-01	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals and families affected with breast and/or ovarian cancer (PMID: 9649133, 12601471, 28205045, 33471991; Leiden Open Variation Database DB-ID BRCA1_002963; Nowlen 2019, dissertation, University of Texas). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV000776317	SCV001169813	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-30	criteria provided, single submitter	clinical testing	The c.1018delG variant, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1018, causing a translational frameshift with a predicted alternate stop codon (p.V340*). This alteration has been reported in numerous breast and/or ovarian cancer families (Eccles DM et al. Br. J. Cancer, 1998 Jun;77:2199-203; Scott CL et al. Hum. Genet., 2003 May;112:542-51; Judkins T et al. Cancer Res. 2005 Nov;65:10096-103; Park B et al. Breast Cancer Res. Treat., 2017 May;163:139-150). Of note, this alteration is also designated as 1137delG in the published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496564	SCV001583933	pathogenic	Hereditary breast ovarian cancer syndrome	2024-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val340*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is also known as 1137delG. ClinVar contains an entry for this variant (Variation ID: 37387). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000030968	SCV004215138	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005016301	SCV005647179	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S	2024-06-22	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000030968	SCV000053559	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000030968	SCV000143984	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496564	SCV000587095	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research